Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTJ5LX2)

• DOT Name: Heterochromatin protein 1-binding protein 3 (HP1BP3)
• Synonyms: Protein HP1-BP74
• Gene Name: HP1BP3
• Related Disease:
  Alzheimer disease
  Brittle cornea syndrome 2
  Postpartum depression
  Progressive pseudorheumatoid arthropathy of childhood
  Schizophrenia
  Advanced cancer
  Neoplasm
• UniProt ID: HP1B3_HUMAN
• PDB ID: 2RQP
• Pfam ID: PF00538
• Sequence:
  MATDTSQGELVHPKALPLIVGAQLIHADKLGEKVEDSTMPIRRTVNSTRETPPKSKLAEG
  EEEKPEPDISSEESVSTVEEQENETPPATSSEAEQPKGEPENEEKEENKSSEETKKDEKD
  QSKEKEKKVKKTIPSWATLSASQLARAQKQTPMASSPRPKMDAILTEAIKACFQKSGASV
  VAIRKYIIHKYPSLELERRGYLLKQALKRELNRGVIKQVKGKGASGSFVVVQKSRKTPQK
  SRNRKNRSSAVDPEPQVKLEDVLPLAFTRLCEPKEASYSLIRKYVSQYYPKLRVDIRPQL
  LKNALQRAVERGQLEQITGKGASGTFQLKKSGEKPLLGGSLMEYAILSAIAAMNEPKTCS
  TTALKKYVLENHPGTNSNYQMHLLKKTLQKCEKNGWMEQISGKGFSGTFQLCFPYYPSPG
  VLFPKKEPDDSRDEDEDEDESSEEDSEDEEPPPKRRLQKKTPAKSPGKAASVKQRGSKPA
  PKVSAAQRGKARPLPKKAPPKAKTPAKKTRPSSTVIKKPSGGSSKKPATSARKEVKLPGK
  GKSTMKKSFRVKK
• Function: Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity. Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Brittle cornea syndrome 2	DISDYP5V	Strong	Genetic Variation	[2]
Postpartum depression	DIS08UKE	Strong	Posttranslational Modification	[3]
Progressive pseudorheumatoid arthropathy of childhood	DISBMRIW	Strong	Posttranslational Modification	[3]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Neoplasm	DISZKGEW	moderate	Biomarker	[5]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[11]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[19]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[14]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[17]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Heterochromatin protein 1-binding protein 3 (HP1BP3).	[13]

References

• [1] Knockdown of heterochromatin protein 1 binding protein 3 recapitulates phenotypic, cellular, and molecular features of aging.Aging Cell. 2019 Feb;18(1):e12886. doi: 10.1111/acel.12886. Epub 2018 Dec 13.
• [2] A role for repressive complexes and H3K9 di-methylation in PRDM5-associated brittle cornea syndrome.Hum Mol Genet. 2015 Dec 1;24(23):6565-79. doi: 10.1093/hmg/ddv345. Epub 2015 Sep 22.
• [3] DNA methylation biomarkers prospectively predict both antenatal and postpartum depression.Psychiatry Res. 2020 Mar;285:112711. doi: 10.1016/j.psychres.2019.112711. Epub 2019 Nov 27.
• [4] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [5] Quantitative profiling of chromatome dynamics reveals a novel role for HP1BP3 in hypoxia-induced oncogenesis.Mol Cell Proteomics. 2014 Dec;13(12):3236-49. doi: 10.1074/mcp.M114.038232. Epub 2014 Aug 6.
• [6] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [13] Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
• [16] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [19] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.